9-92001508-C-T

Variant names:

• chr9-92001508-C-T
• rs7042102
• ENST00000642671.1:n.*1756-102G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642671.1(SPTLC1):​n.*1756-102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,106 control chromosomes in the GnomAD database, including 24,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (24787 hom., cov: 32)
  • Exomes 𝑓: 0.46 (4 hom.)
• Consequence: SPTLC1 ENST00000642671.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

SPTLC1 (HGNC:11277): (serine palmitoyltransferase long chain base subunit 1) This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]

LOC107987094 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107987094	XR_001746834.2	n.480-102G>A		intron_variant	Intron 1 of 2
LOC107987094	XR_001746835.2	n.480-102G>A		intron_variant	Intron 1 of 3
LOC107987094	XR_001746836.2	n.480-102G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000642671.1	n.*1756-102G>A		intron_variant	Intron 16 of 16			ENSP00000495764.1
SPTLC1	ENST00000643599.1	n.*1495-102G>A		intron_variant	Intron 13 of 15			ENSP00000494770.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81004 AN: 151962 Hom.: 24737 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.462 AC: 12 AN: 26 Hom.: 4 AF XY: 0.444 AC XY: 8 AN XY: 18

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.458

GnomAD4 genome AF: 0.533 AC: 81115 AN: 152080 Hom.: 24787 Cov.: 32 AF XY: 0.533 AC XY: 39658 AN XY: 74336

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.497

Alfa AF: 0.439 Hom.: 7915

Bravo AF: 0.560

Asia WGS AF: 0.489 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7042102; hg19: chr9-94763790; COSMIC: COSV69733581;